Modeling By Considering Change Of Material Properties And Quality Control For Circulating Fluidized Bed Granulation Process

Drug production is an important part of the national economy,and circulating fluidized bed granulation process is an important part of the drug production process.During the drug development phase,due to the adjustment of the drug formulation,caused changes in the properties of raw materials,resulting in a new formula or raw material properties under the conditions of circulating fluidized bed granulation process without historical data and operational experience,making process modeling and particle quality index control facing challenge.Repeated experiments to explore the operating conditions resulting in problems of low efficiency and waste of raw materials.Therefore,considering the change of the properties of raw materials,the research of granulation process modeling and optimization control has important theoretical and practical significance.This thesis first introduced the circulating fluidized bed granulation process and operating principle,analysis the main factors and granulation process of particle growth mechanism,and introduced the granulation process commonly used materials and adhesives.Then,According to the principle of mass conservation,conservation of momentum and conservation of quantity,a mechanism model of circulating fluidized bed granulation process with binder viscosity,initial particle density and particle size distribution was established based on single-region population balance model.The research group proposed to use the existing predictive model of the droplet diameter of the binder solution to convert the amount of indirect manipulated variable droplet addition to the direct manipulated variable binder mass addition rate and to introduce the atomization pressure and the nozzle intake rate to the mechanism model,And through the adhesive viscosity model to achieve the viscosity of the adhesive as well as the particle size distribution and density of raw and auxiliary materials,and then set up a singlearea mechanism model of the circulating fluidized bed granulation process considering the change of the properties of the raw materials.Through the simulation study,the established mechanism model can reflect the influence of the operation variables and the change of the material properties on the final particle quality,and verify the validity of the mechanism model.Due to the inhomogeneous particle motion within the fluidized bed,the fluidized bed can be divided into two well-mixed and stable zones depending on whether or not it is in contact with the binder.On this basis,the research group established a two-zone mechanism model of circulating fluidized bed considering the variation of material properties based on the two-zone population equilibrium model.The particle volume in both regions and the rate of particle volume exchange between regions in this model were calculated using computational fluid dynamics(CFD)simulations.The simulation results verify the validity of the two-region mechanism model.In view of the change of the raw material properties caused by the change of the prescription during the drug development phase,the problem of the quality control of the particles under the new raw material properties is difficult to be achieved,based on the established mechanism model,the research group realized the particle quality control based on the data driven optimal iterative control method.The simulation results show the effectiveness of the method.